Defibrillation shock strength determination technology

ABSTRACT

A method for determining a cardiac shock strength, for example the programmed first-therapeutic shock strength of an implantable cardioverter defibrillator (ICD), including the steps of sensing a change in a T-wave of an electrogram with respect to time such as the maximum of the first derivative of a T-wave of an electrogram; delivering a test shock by (i) delivering a test shock at a test-shock strength and at a test-shock time relating to the maximum of the first derivative of the T-wave with respect to time; and (ii) sensing for cardiac fibrillation. If fibrillation is not sensed, test-shock delivery is repeated at the same test-shock strength and at specific, different test-shock times relating to the maximum of the first derivative of the T-wave. If fibrillation is still not sensed, the shock strength is decreased and test shocks are repeated at the same specific test shock times relative to the maximum of the first derivative of the T-wave. And if fibrillation is sensed, the programmed therapeutic shock strength of the ICD is set as a function of the incrementally greater test-shock strength. Also disclosed is an apparatus for selecting a programmed first-shock strength of an ICD, including a shock subsystem for delivering therapeutic shocks and test shocks to the heart, and a ULV subsystem connected to the shock subsystem, to provide test shocks of test-shock strengths and at test-shock times relating to the maximum of the first derivative of the T-wave with respect to time, and to determine the therapeutic shock strength of the ICD as a function of the test-shock strengths.

CROSS-REFERENCE TO RELATED APPLICATIONS, IF ANY

[0001] This application claims the benefit under 35 U.S.C. §119(e) ofco-pending U.S. Provisional Patent Application Serial No. 60/372,402,filed Apr. 15, 2002, which is hereby incorporated by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

[0002] Not applicable.

REFERENCE TO A MICROFICHE APPENDIX, IF ANY

[0003] Not applicable.

BACKGROUND OF THE INVENTION

[0004] 1. Field of the Invention

[0005] The present invention relates, generally, to implantablecardioverter defibrillators (ICDs) and defibrillation methods, andparticularly to a method and apparatus for determining the optimal shockstrength for defibrillation, and most particularly to determining theupper limit of vulnerability (ULV) based on changes with respect to timein the T-wave of the cardiac signal, preferably the maximum of the firstderivative of the T-wave with respect to time measured preferablyexclusively from implanted electrodes. Unless otherwise indicated, theterm “derivative of the T-wave” refers to the first derivative of theT-wave with respect to time. The technology is useful for automating theprocess of selecting the first defibrillation shock strength for ICDs.

[0006] 2. Background Information.

[0007] Heart disease is a leading cause of death in the United States.The most common form of cardiac death is sudden, caused by cardiacrhythm disturbances (arrhythmias) in the form of a ventriculartachycardia or ventricular fibrillation.

[0008] Ventricular tachycardia is an organized arrhythmia originating inthe ventricles. It results in cardiac contractions that are too fast ortoo weak to pump blood effectively. Ventricular fibrillation is achaotic rhythm disturbance originating in the ventricles that causesuncoordinated cardiac contractions that are incapable of pumping anyblood. In both ventricular tachycardia and ventricular fibrillation, thevictim will most likely die of “sudden cardiac death” if the normalcardiac rhythm is not reestablished within a few minutes.

[0009] Implantable cardioverter defibrillators (ICDs) were developed toprevent sudden cardiac death in high risk patients. In general, an ICDsystem consists of implanted electrodes and a pulse generator thathouses implanted electrical components. The ICD uses implantedelectrodes to sense cardiac electrical signals, determine the cardiacrhythm from these sensed signals, and deliver an electrical shock to theheart if life-threatening ventricular tachycardia or ventricularfibrillation is present. This shock must be of sufficient strength todefibrillate the heart by simultaneously depolarizing all or nearly allheart tissue. Shock strength is typically measured as shock energy inJoules (J). The defibrillating shock interrupts the abnormal electricalcircuits of ventricular tachycardia or ventricular fibrillation, therebypermitting the patient's underlying normal rhythm to be reestablished.ICD pulse generators are implanted within the patient and connected tothe heart through electrodes to provide continuous monitoring andimmediate shocking when a life-threatening rhythm disturbance isdetected. Because the devices must be small enough for convenientimplantation, ICDs are limited in their ability to store electricalenergy. In general, ventricular tachycardia can be terminated by weakershocks than those required to terminate ventricular fibrillation. ThusICDs must deliver a sufficiently strong shock to insure reliabledefibrillation in response to each occurrence of ventricularfibrillation.

[0010] One method is to use the maximum shock strength of the ICD foreach shock. However, this approach is an inefficient use of the ICD'slimited stored electrical energy and will unnecessarily reduce theuseful life of an ICD pulse generator.

[0011] It is well known in the art that the shock strength required todefibrillate a human heart effectively varies with the implanted leadconfiguration and placement as well as the individual heart'sresponsiveness to the shock. To maximize efficiency of an ICD system,the minimum shock strength necessary to defibrillate an individualpatient's heart reliably must be determined.

[0012] However, it is also well known in the art that the relationshipbetween an ICD's defibrillation shock strength and success or failure ofdefibrillation is represented by a probability-of-success curve ratherthan an all-or-none defibrillation threshold (DFT). Very weak, lowstrength (low energy) shocks never defibrillate. Very strong shocks, atenergies greater than the maximum output of ICDs, always defibrillate.However, clinically relevant shock strengths for ICDs lie between thesetwo extremes. In this intermediate range of shock strengths, a shock ofa given strength may defibrillate successfully on one attempt and not onanother attempt.

[0013] Determining a complete curve of the probability of success forevery possible shock strength requires many fibrillation-defibrillationepisodes. In clinical (human) studies and procedures, the number offibrillation-defibrillation episodes should be limited because of theirassociated risks. Thus the goal of testing at the time of ICD implantcannot be to determine a complete probability of success curve. Ingeneral, the goal of testing at ICD implant is to provide an accurateestimate of the minimum shock strength that defibrillates with a highprobability of success while using a minimum amount of testing. Theshock energy that defibrillates with an X % probability of success isreferred to as the defibrillation thresholds or DFT_(x). Thus a goal ofclinical testing at ICD implantation is to estimate a shock strength inthe range of the DFT₉₅-DFT₉₉. This is the optimal strength at which toprogram the first shock of an ICD. For research purposes, it may bepreferable to estimate the DFT₅₀.

[0014] The minimum measured shock strength that defibrillates during agiven session of defibrillation testing is referred to, in general, bythe term DFT, despite the fact that no true threshold for defibrillationexists. All methods for determining the DFT of an ICD system requireinducing fibrillation a number of times and testing various shockstrengths for defibrillation through the implanted defibrillation leads.In the commonly used step-down method defibrillation is attempted at ahigh shock strength that is likely to defibrillate the heartsuccessfully. If this shock is unsuccessful, a stronger “rescue shock”is delivered to effect defibrillation. Regardless of the outcome of thedefibrillation shock, there is a waiting period of about 5 minutes topermit the patient's heart to recover. If the defibrillation shock issuccessful, fibrillation is reinitiated and the defibrillation isattempted at a lower shock strength. This process is repeated withsuccessively lower defibrillation shock energies until the shock doesnot defibrillate the heart. The minimum shock strength thatdefibrillates is the DFT. Depending on the initial shock strength, theDFT determined in this manner is usually between the DFT₃₀ and DFT₇₀.The ICD is then programmed to a first-shock strength selected to be anestimate of the lowest value that can reliably achieve defibrillation byadding an empirically-determined safety margin to the DFT.

[0015] Other methods for determining the DFT require additionalfibrillation-defibrillation episodes after a defibrillation shock hasfailed. In these methods, fibrillation is reinitiated after a faileddefibrillation shock and defibrillation is attempted at successivelyhigher shock strengths until a shock defibrillates the heartsuccessfully. This change from a shock strength that does notdefibrillate to one that does (or vice versa) is called a reversal ofresponse. DFT methods may require a fixed number of reversals. If thesize of the shock increments and decrements is the same, amultiple-reversal (up-down) method provides a good estimate of theDFT₅₀. An alternative Bayesian method uses a predetermined number ofunequal shock increment steps and decrement steps to estimate anarbitrary, specific point on the DFT probability of success curve.

[0016] One significant disadvantage of all DFT methods is the necessityto repeatedly fibrillate and then defibrillate the patient's heart todetermine the DFT. For example, U.S. Pat. No. 5,531,770 describes amethod of DFT testing that is described as an advantage because itlimits the number of fibrillation-defibrillation episodes to 5, incontrast to other methods such as the “three-reversal” method that mayrequire more episodes. These repeated episodes of fibrillation anddefibrillation may have an adverse effect on the patient. Further, eachfibrillation episode is associated with a small risk that the patientcannot be defibrillated and will thus die. Considerable time must bespent between test cycles in order to provide the patient's heart timeto recover from the previous round of fibrillation-defibrillation.

[0017] A second disadvantage is that successful defibrillation is aprobability function of shock energy, not an all or none phenomenondescribed by a simple threshold. Since the usual clinical DFT methodresults in a measurement somewhere in the broad range between the DFT₃₀and DFT₇₀, optimal ICD programming cannot be achieved by adding a singleempirically-determined shock increment. The resulting programmed firstshock strength sometimes results in selecting a shock that either doesnot defibrillate reliably or unnecessarily uses excessive energy.

[0018] It is known in the art that shocks delivered during thevulnerable period of the normal cardiac cycle induce ventricularfibrillation, providing that the shock energy is greater than a minimumvalue and less than a maximum value. The ULV is the shock strength at orabove which fibrillation is not induced when a shock is delivered duringthe vulnerable period of the normal cardiac cycle. The ULV may bedisplayed graphically as the peak of the vulnerable zone, a boundedregion in a two-dimensional space defined by coupling interval (time) onthe abscissa and shock strength on the ordinate. The ULV, which can bemeasured in regular rhythm, corresponds to a shock strength thatdefibrillates with a high probability of success and correlates stronglywith the DFT. Because the ULV can be determined with a singlefibrillation-defibrillation episode, it has the potential to provide apatient-specific measure of defibrillation efficacy that requires fewerfibrillation-defibrillation episodes than DFT testing.

[0019] Although the vulnerable period occurs generally during the T-waveof the surface electrocardiogram (ECG), its precise timing varies fromindividual to individual. More importantly, the peak of the vulnerablezone, which corresponds to the most vulnerable time intervals in thecardiac cycle, also varies from individual to individual. Accuratedetermination of the ULV depends critically delivering a T-wave shock atthe peak of the vulnerable zone.

[0020] Several methods of determining the defibrillation shock strengthfor ICDs are based on the ULV. One such method is disclosed in U.S. Pat.No. 5,105,809. This method begins by applying an initial electricalshock to the patient's heart during the vulnerable period. The shock istimed during the “occurrence of the T-wave.” The shock strength of theinitial shock is sufficiently high so as to have a low probability ofinitiating fibrillation. Assuming this initial shock fails to inducefibrillation, a second shock of less magnitude is delivered with thesame timing during a subsequent vulnerability period. The process isrepeated with successive shocks of lesser magnitudes until fibrillationis induced. When fibrillation finally occurs, the energy of thepreceding shock that did not cause fibrillation is the shock strengthrequired to defibrillate. This method does not disclose how the singleshock at each energy is timed to coincide with the peak of thevulnerable zone. Indeed, it does not mention the peak or most vulnerabletime in the vulnerable zone.

[0021] Another method for establishing a ULV is disclosed in U.S. Pat.No. 5,346,506. The method relies on research demonstrating that the 56%probability of successful defibrillation can be approximated bydetermining the 50% probability that a shock exceeds the ULV. A shock isapplied to the heart through epicardial patches at a predeterminedlimited period of time centered on the mid-upslope of the T-wave. Thedisclosure argues that the total number of shocks is reduced by nothaving to scan the entire T-wave with shocks. A disadvantage of thismethod is that the shock strength for the first application must beestimated beforehand. The number of shocks required to determine the DFTis reduced only if the estimated 50% probability of reaching the ULV isquite accurate. Further, this method requires multiplefibrillation-defibrillation episodes, with their attendant risks, toprovide an accurate estimate of the shock energy required to achieve a50% probability of successful defibrillation.

[0022] U.S. Pat. No. 5,954,753 discloses that the ULV can be determinedby one or two T-wave shocks timed near the peak of the T-wave,preferably about 10% of the QT interval or 30 ms before the peak.

[0023] The methods described in U.S. Pat. No. 5,105,809, U.S. Pat. No.5,346,506, and U.S. Pat. No. 5,954,753 depend critically on accurate, apriori knowledge of the timing of the peak of the vulnerable zonebecause shocks are delivered at only one or two time intervals. Becausethe timing of this peak differs relative to any fixed point in theT-wave from patient to patient, it is not necessarily contemporaneouswith any single timing interval based on the T-wave. As a result, thesemethods are susceptible to error because the specific time during theT-wave at which shocks are delivered may have substantially lessvulnerability than peak of the vulnerable zone. If T-wave shocks are notdelivered at the peak of the vulnerable zone, the ULV will beunderestimated. This discrepancy will not be appreciated at the time ofimplantation and therefore these methods may substantially underestimatethe required defibrillation shock energy setting.

[0024] Further, as will be seen in the discussion of U.S. Pat. No.5,564,422 below, U.S. Pat. No. 5,954,753 does not identify the peak ofthe vulnerable zone relative to the peak of the T-wave since theinterval it teaches for timing of T-wave shocks is shorter than the mostvulnerable intervals for typical clinically-used transvenous ICDsystems.

[0025] U.S. Pat. No. 5,564,422 to Chen and Swerdlow, which isincorporated by reference, usually provides a reliable estimate of theDFT for the clinical purpose of implanting an ICD for two-electrodetransvenous defibrillation systems. However, such systems are no longerin widespread use. However, in practice, the method and apparatusdisclosed in this patent has been found to require measuring andanalyzing multiple surface ECG leads. The method and apparatus disclosedin this patent cannot be performed using intra-cardiac leadsexclusively.

[0026] The Chen and Swerdlow method bases the timing of T-wave shocks onthe latest-peaking monophasic T-wave recorded from the surface ECG. Thetiming of the peak of the T-wave varies substantially among ECG leads asa consequence of QT-interval dispersion. In different patients, thelatest-peaking monophasic T-wave occurs unpredictably in various surfaceECG leads. Even a small error in measuring the pacer spike to peakinterval of the latest-peaking monophasic T-wave can result in errors inthe measured ULV and thus compromise its value as a clinical tool. Thus,to be used accurately, this method requires measurement and analysis ofintervals from multiple (preferably all 12) standard surface ECG leadsto identify the lead with the latest-peaking monophasic T-wave.

[0027] The Chen and Swerdlow method cannot be performed using ECGsrecorded exclusively from implanted electrodes (electrograms). Implantedelectrodes, particularly those including intra-cardiac electrodes, oftenhave biphasic rather than monophasic T-waves as shown in FIG. 3. Whenthis occurs, the peak of the (monophasic) T-wave is undefined and thismethod cannot be applied. Further, even if an intra-cardiac electrodehas a monophasic T-wave, the peak may precede that of a surface ECGlead.

[0028] This limitation also applies to the method of U.S. Pat. No.5,954,753 which depends on identification of the peak of the T-wave.This method recommends identification of the peak of T-waves recordedfrom ICD electrograms, which usually have biphasic T-waves. FIG. 3Ashows that the peak of the latest-peaking monophasic T-wave on thesurface ECG agrees closely with the peak of the derivative of theintracardiac electrogram, but not with the peak of the biphasicintracardiac electrogram. Further, as FIG. 3A shows, the T-wave recordedfrom an intracardiac electrogram often is low in amplitude. Thusidentification of its peak may be subject to significant measurementerror.

[0029] The present invention differs from the Chen and Swerdlow (U.S.Pat. No. 5,564,422) method in several respects, including but notlimited to, that the coupling interval of T-wave shocks is based on thepoint of maximum derivative of the repolarization phase (T-wave) of anelectrogram recorded from an implanted electrode, whether the T-wave isbiphasic or monophasic. This approach involves the concept of theactivation-recovery interval. The activation-recovery interval is theinterval between the times of minimum derivative of the ventricularelectrogram and maximum derivative of the T-wave in a unipolarintra-cardiac electrogram. Theoretical analysis predicts that maximumderivative of the T-wave is proportional to a spatial weighting functionof the third temporal derivative of the cardiac action potential.Because the maximum of the first temporal derivative of the actionpotential times very closely with the maximum of its third temporalderivative, the activation-recovery interval has been used as a measureof local repolarization in basic physiologic studies. Because theactivation-recovery interval acts as a spatial average, it is dominatedby the action potentials of cells closest to the recording site. Theactivation-recovery interval recorded from a point, intra-cardiacelectrode has been used to assess local repolarization. For example, ithas been used to assess dispersion of local repolarization intervals incanines and local effects of catheter ablation in humans.

[0030] In an embodiment of the present invention, the analyzedelectrogram may be recorded from large extra-cardiac or intra-cardiacelectrodes. Recordings from these large electrodes contain moreinformation regarding global repolarization than recordings from pointelectrodes.

[0031] An additional limitation of the method of Chen and Swerdlow (U.S.Pat. No. 5,564,422) is that the timing of the latest peaking T-wave ismeasured only once at the beginning of testing. Research has shown thatthe interval between the pacer spike and the peak of the latest peakingT-wave may change over time during the testing procedure as a result ofshock delivery. Since the method of Chen and Swerdlow (U.S. Pat. No.5,564,422) sets the timing of all subsequent shocks by using the initialmeasurement of the interval between the pacer spike and peak of thelatest-peaking monophasic T-wave, subsequent shocks may not be deliveredat the desired time relative to the peak of the latest peaking T-wave atthe moment the shock is delivered. Even a small error in measuring thepacer spike to peak interval of the latest-peaking monophasic T-wave (ofthe order introduced by post-shock changes that occur during clinicaltesting after several shocks) can result in errors in the measured ULVand thus compromise its value as a clinical tool. (Swerdlow C D, MartinD J, Kass R M, Davie S, Mandel W J, Gang E S, Chen P S. The zone ofvulnerability to T-wave shocks in humans. J. Cardiovasc Electrophysiol.1997;8:145-54.) An embodiment of the method of the present inventionavoids such errors by re-measuring the pacer spike to peak interval ofthe derivative of the intra-cardiac T-wave automatically after eachshock.

[0032] A further limitation of the method of Chen and Swerdlow (U.S.Pat. No. 5,564,422) is that it does not scan the vulnerable zonecompletely for the defibrillation electrode configuration most commonlyused in clinical practice today. This may lead to underestimation of theULV in some patients, which in turn may lead to programming ofinsufficient first ICD shock strengths and failed defibrillations. Themethod of Chen and Swerdlow usually provides an adequate scan of thevulnerable zone when shocks are delivered using a two-electrode systemfrom right-ventricular coil to left-pectoral ICD case (also referred toas the “housing” or “can”). (Swerdlow C D, Martin D J, Kass R M, DavieS, Mandel W J, Gang E S, and Chen P S, in The Zone of Vulnerability toT-wave shocks in Humans, J Cardiovasc Electrophysiol. 1997; 8:145-54).However, in present ICDs, the principal shock pathway uses a differentthree-electrode system to deliver shocks from right-ventricular coil toleft-pectoral case plus a superior vena cava electrode. It providessuperior defibrillation to the two-electrode system. Recently theinventor has demonstrated that the peak of the vulnerable zone usingthis three-electrode defibrillation configuration may not be at any ofthe intervals tested in the method of Chen and Swerdlow (U.S. Pat. No.5,564,422) or those tested in the method of U.S. Pat. No. 5,954,753.Instead the most vulnerable intervals time after the peak of the latestpeaking T-wave in some patients. In fact, in 5 of 25 patients tested(20%), the peak of the vulnerable zone occurred at least 20 ms beyondthe peak of the latest peaking T-wave. In these patients, the methods ofU.S. Pat. No. 5,564,422 and U.S. Pat. No. 5,954,753 do not accuratelyidentified the ULV.

[0033] In one embodiment of the present invention, four shocks are usedto scan the vulnerable zone reliably in humans. When the surface ECG isused as a reference, these shocks should be delivered at −40 ms, −20 ms,0 ms, and +20 ms relative to the peak of the latest-peaking monophasicT-wave. Clinical application of this four-shock method with T-waveshocks timed relative to the surface ECG has resulted in programming ofshock strengths that defibrillate with near uniform success for bothtwo-electrode and three-electrode defibrillation configurations.Research has demonstrated that the shock strength equal to the step-downULV determined by the present invention, successfully defibrillates 90%of the time with a 95% confidence level of plus or minus 8%. When theshock strength is increased to a value that is 3 Joules above themeasured ULV, the rate of successful defibrillation is 100% with aconfidence level greater than 95%.

[0034] For the present, standard three-electrode right-ventricular coilto left-pectoral case plus a superior vena cava shock pathway, threeshocks at −20 ms, 0 ms, and +20 ms relative to the peak of thelatest-peaking monophasic T-wave correctly identified the mostvulnerable intervals in all 25 of 25 patients tested (100%). In the samepatients, if shocks were timed relative to the maximum of the derivativeof the T-wave, four shocks timed at −20 ms, 0 ms, and +20 ms, and +40 mswere required to identify the most vulnerable intervals in 24 of 25patients (96%). In the remaining patient, the T-wave scan missed themost vulnerable interval by 9 ms. Thus, for the three-electrode shockpathway an alternative embodiment delivers up to three test shocks at−20 ms, 0 ms, and +20 ms relative to the peak of the latest-peakingmonophasic surface T-wave. A second alternative embodiment for thisthree-electrode shock pathways delivers up to four test shocks at −20ms, 0 ms, and +20 ms, and +40 ms relative to the maximum of thederivative of the T-wave of the ICD electrogram.

[0035] All US patents and patent applications, and all other publisheddocuments mentioned anywhere in this application are incorporated byreference in their entirety.

BRIEF SUMMARY OF THE INVENTION

[0036] The present invention provides an automatic ICD system and methodwhich is practical, reliable, accurate, and efficient, and which isbelieved to fulfill the need and to constitute an improvement over thebackground technology. The system and method quickly and accuratelydetermines the optimal first shock strength of an ICD system for apatient by evaluating the heart's ULV during or after implantation. Asnoted above, the ULV, if measured correctly, correlates closely with ashock strength that defibrillates with a high probability of success.

[0037] The system and method of the present invention involve deliveringone or a series of shocks to the heart in paced or native rhythm. Theshocks are timed in relation to a change with respect to time in theT-wave of a cardiac signal. Preferably, the signal is an electrogramrecorded from totally-implanted electrodes. Preferably the change withrespect to time is the first, ordinary derivative with respect to timeof the T-wave.

[0038] Methods and rationale for the determination and manipulation ofordinary derivatives of single or multi-dimensional functions tounderstand the complexities of change or variation as it occurs acrossthe range of one or more independent variables are well-known in theart. The ordinary derivative for a single function is well-known torepresent local changes or variations, and there exists many methods todetermine the position of these local changes with respect to a set ofvalues for an independent variable.

[0039] For example, as it relates to the present invention, a singledimensional function comprises electrogram or ECG data sampled from apatient over a period of time that represents the patient's cardiaccycle. The derivative of this function with respect to time over thecourse of a predetermined single cardiac cycle is a function thatrepresents a set of local changes or variations that occurred in theelectrogram or ECG function during that time period. A second derivativefunction of this derivative function further determines local changes inthe first derivative across the time period, and represents additionalinformation regarding changes in the electrogram or ECG function.

[0040] Iterating the process of derivatives of derivatives captures thetotality of information in a function regarding the changes orvariations that occurs in the function over the range of an independentvariable. Functions that are constructed using the iterative process arecalled second (2^(nd)) derivatives, third (3^(rd)) derivatives, fourth(4^(th)) derivatives, n^(th) derivatives, and so on. These methods canbe applied to multi-dimensional functions and these methods are furtherdeveloped to provide partial derivatives, which determine local changesin a multi-dimensional function as these changes related to a subset ofthe independent variables.

[0041] There are well-known methods that further differentiate theselocal changes or variations into various types or kinds of changes. Forexample, a local change in a function may indicate whether the functionhas a local minimum, local maximum, or local saddle point at a value ofan independent variable. A local minimum and a local maximum are calledextreme points for the function. For example, a local maximum of an ECGfunction during a T-wave indicates a point at which cardiac-relatedrepolarization changes cause the largest change in a patient'siso-electric potential as it is measured using an ECG device.Furthermore, a local maximum and a local minimum of a derivative of anECG function during a T-wave can indicate points at which the localchanges during the cardiac-related repolarization are changing orvarying at the highest rates.

[0042] Furthermore, there are well methods for easily determining theselocal changes or variations in a function or one of its derivatives. Forexample, a local maximum for a function is a value of the function at apoint A such that f(A)≧f(x) for all other values x of the independentvariable near the value A. A local minimum for a function is a value ofthe function at a point A such that f(A)≦f(x) for all other values x ofthe independent variable near the value A. The set of local maximums andminimums are quickly determined by taking the derivative of thefunction, determining the independent variable values for which thefunction's derivative is zero (called critical numbers), and applyingthe test described above to each of these values.

[0043] There are many different types of derivatives (or differentials)as well that may be applied to a function to determine informationregarding a local change in the function, depending on thedimensionality and complexity of the function. An important subset ofthese different types of derivatives comprises a directional derivative,a partial derivative, an implicit differential, a variance calculation,a bounded variation calculation, a tangent vector approximation, and thefirst order differential operators from vector calculus such as div,grad, and curl.

[0044] The theory and application of derivatives are most applicable tofunctions that are modeled as continuous functions. Functions used bymethods and apparatus that construct these functions from sampled dataas a part of the invention operation are discrete functions that areappropriately modeled by continuous functions, and it is well-known thatthe methods for continuous functions can be applied to them. Suchfunctions are called discrete analogs for continuous functions, and assuch all the derivative and differential methods have appropriatediscrete analogs that are applied to these functions to determine thetotality of information as the information is reflected by changes inthe functions previously described.

[0045] For example, an important discrete analog methodology that iswell-known and is applicable to discrete function analogs of continuousfunctions is the method of finite differences. The entirety of thefamily of derivatives and differentials are accurately approximated byfinite difference methods, particularly those methods that are based onthe method of Taylor Series expansion for a function. For example, firstderivatives are well approximated using the forward difference, backwarddifference, or central difference Taylor Series expansion methods. Othersimilar methods are the linear approximation methods that constructtangent and secant lines in relation to the point of local change orvariation.

[0046] In one embodiment, the ULV is determined by shocking the heart ata series of predetermined times in relation to the first temporalderivative of the T-wave and at increasing or decreasing test-shockstrengths. The lowest shock strength which fails to induce fibrillationis determined to be the ULV. The optimal first shock strength forprogramming an ICD is predicted to be incrementally greater than the ULVby about 5 J. In a second embodiment, a vulnerability safety marginmethod, the heart is shocked at a series of predetermined times inrelation to the first temporal derivative of the T-wave, but only at asingle test shock energy. If fibrillation is not induced, a safe shockstrength is predicted to be incrementally greater than tested shockstrength by about 5 J. This safety-margin approach does not determinethe minimum (optimal) safe shock strength, but rather only ensures thatthe programmed shock strength is sufficient. The advantages of thesafety margin method are that a sufficient first shock strength for ICDscan be determined without inducing fibrillation and that only three tofour test shocks are required. Research has shown that programming firstICD shocks to 5 J above the shock strength tested in this vulnerabilitysafety-margin strategy resulted in a first-shock success rate as good asor better than those reported for other methods of implant testing.Research has also shown that this strategy, which does not requireinduction of fibrillation, can be applied to at least 80% of ICDrecipients. (Swerdlow CD. Implantation of cardioverter defibrillatorswithout induction of ventricular fibrillation. Circulation.2001;103:2159-64.)

[0047] In another embodiment, the intra-cardiac electrogram used fordetermining the derivative of the T-wave is recorded between one (ormore) large intra-cardiac electrode(s) such as defibrillation coils andone (or more) extra-cardiac electrodes such as the ICD housing (commonlyreferred to as a “case” or “can”) or the ICD housing coupled to anotherdefibrillation electrode such as a defibrillation coil in the superiorvena cava.

[0048] Regarding the method of the invention, one particular aspect isfor determining a therapeutic cardiac shock strength for defibrillation,comprises the steps of:

[0049] (a) sensing a change with respect to time in the T-wave of acardiac signal;

[0050] (b) delivering a test shock by:

[0051] (i) delivering a test shock at a test-shock strength and at atest-shock time relating to the change with respect to time of theT-wave; and

[0052] (ii) sensing for cardiac fibrillation; and

[0053] (c) if fibrillation is not sensed, repeating step (b) at thetest-shock strength and at a different test-shock time relating to thechange with respect to time of the T-wave; and

[0054] (d) if fibrillation is sensed, setting the therapeutic cardiacshock strength as a function of the test-shock strength.

[0055] A more specific aspect of the method for determining an optimalprogrammed first-shock strength of an ICD relative to the ULV, the ICDhaving at least one sensing electrode and at least one shockingelectrode, comprises the steps of:

[0056] (a) setting an initial test-shock strength, four offset times,and a shock strength decrement;

[0057] (b) delivering a set of up to four test shocks with the ICD tothe patient, each test shock member of the set of test shocks comprisingthe sub-steps of:

[0058] (i) sensing an electrogram from the patient;

[0059] (ii) detecting at least one predetermined base timing point priorto the T-wave of the electrogram;

[0060] (iii) differentiating the electrogram;

[0061] (iv) detecting at least one maximum of the derivative of aT-wave;

[0062] (v) measuring at least one base time interval from the at leastone base timing point to the at least one maximum derivative of aT-wave;

[0063] (vi) delivering a test shock to the patient at the test-shockstrength and at a test-shock time corresponding to the base timeinterval plus one of the offset times;

[0064] (vii) sensing for an induction of fibrillation for apredetermined sensing time period; and

[0065] (viii) if fibrillation is not sensed in step b(vii), thenrepeating sub-steps b(i-vii), at the same test-shock strength, up to thefourth test shock, each test shock member of the set of test shockshaving a different test-shock time corresponding to a base time intervalplus an offset time; and

[0066] (c) if fibrillation is not sensed in step (b) by the fourth testshock, then repeating step (b) at a lower test-shock strengthcorresponding to the shock strength decrement, to deliver at least oneadditional set of up to four test shocks; and

[0067] (d) if fibrillation is sensed in step (b), then:

[0068] (i) defibrillating the patient; and

[0069] (ii) setting the programmed first-shock strength of an ICD at apredetermined higher level than the test-shock strength at whichfibrillation was induced.

[0070] Regarding the apparatus of the invention, one aspect is anoverall ICD system which delivers an optimal therapeutic cardiac shock,comprising:

[0071] (a) a plurality of electrodes, at least one electrode beingadapted for sensing cardiac signals and at least one electrode beingadapted for delivering shocks to the heart;

[0072] (b) a shock subsystem connected to the at least one electrode fordelivering shocks and which is capable of generating test shocks andtherapeutic cardiac shocks; and

[0073] (c) a ULV subsystem connected to the shock subsystem and forproviding test shock information to the shock subsystem, the test shockinformation including test-shock strength and test-shock time relatingto a change in cardiac signals with respect to time, and for determiningthe shock strength of the therapeutic cardiac shocks as a function ofthe test shock strength.

[0074] Another aspect of the apparatus is a ULV subsystem fordetermining a therapeutic cardiac shock strength, for example with anexisting ICD, comprising:

[0075] (a) a sensor for sensing the electrical activity of the heart,including a change with respect to time of the T-wave of a cardiacsignal and including the presence of fibrillation;

[0076] (b) a test-shock driver for transmitting time and strengthinformation regarding test-shocks;

[0077] (c) a controller to determine the cardiac shock strength as afunction of the response (fibrillation or no fibrillation) totest-shocks of varying strengths and times.

[0078] A more specific aspect of the apparatus is an ICD system fordetermining and providing an optimal programmed first-shock strengthbased on the upper limit of vulnerability, comprising:

[0079] (a) a plurality of implantable electrodes; and

[0080] (b) a shock delivery subsystem for generating and deliveringshocks, connected to the electrodes; and

[0081] (c) a ULV subsystem comprising;

[0082] i) a sensor, connected to the electrodes, for sensing theelectrical activity of the heart, including a change with respect totime of the T-wave of a cardiac signal and including the presence offibrillation;

[0083] ii) a timer connected to the sensor for providing a series ofshock times, timed relative to the maximum derivative of the T-wave;

[0084] iii) a test shock driver, connected to the timer, fortransmitting timing and amplitude information regarding T-wave, testshocks;

[0085] iv) a memory unit, connected to the test shock driver and theshock subsystem, for storing programmable values such as pacing cyclelength, timing intervals, an initial shock strength, and values forincrementing and decrementing shock strength; and

[0086] iv) a controller, connected to the sensor, test-shock driver, andshock subsystem for incrementally varying shock strength and the shocktimes, whereby the system provides a test shock having a shock strengthand shock time selected by the controller, the shock subsystemdelivering an initial test shock to the heart at an initial shockstrength and an initial shock time and delivering subsequent test shocksto the heart by varying the shock and decreasing the shock strength, astrength decrement, until the heart is induced to fibrillate, wherebythe shock strength of the test shock immediately prior to the test shockthat induces fibrillation represents the ULV.

[0087] The features, benefits and objects of the invention will becomeclear to those skilled in the art by reference to the followingdescription, claims and drawings.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING

[0088]FIG. 1 is an anterior sectional view of a human heart in relativeanatomical position, depicting the relative positioning of intravascularelectrode catheters and an ICD according to the present invention.

[0089]FIG. 2 is a schematic block diagram depicting a suitablearrangement for an ICD according to the present invention.

[0090]FIG. 3A. is an actual recording of ECG lead II, an intracardiacelectrogram (EGM), and its first time derivative (EGM dV/dt).

[0091]FIG. 3B is a timing diagram that represents an expanded version ofthe lower two panels in FIG. 3A. It depicts the relationship between apaced cardiac cycle and test electrical shocks in accordance with apreferred embodiment of the present invention. The upper panel in FIG.3B depicts an intra-cardiac electrogram, and the lower panel depicts itsfirst time derivative.

[0092]FIG. 4 is a diagram illustrating how the timing of test shocks isdetermined from the derivatives of an intra-cardiac electrogram for asequence of test shocks at a single shock energy in accordance with anembodiment of the invention. Each row displays the timing measurementand corresponding shock delivery time for a single test shock.

[0093]FIG. 5 is a block diagram depicting a sequence of steps inaccordance with a preferred embodiment of the method and system of thepresent invention.

[0094]FIG. 6 is a graph that compares the timing of the peak of thelatest peaking monophasic T-wave on the surface ECG with the timing ofthe maximum derivative of the T-wave determined from ICD electrodes.

[0095]FIG. 7. shows the timing of the most vulnerable intervals,representing the peak of the vulnerable zone, in relation to the timingof the maximum derivative of the T-wave determined from ICD electrodes.

DETAILED DESCRIPTION

[0096] Referring to FIG. 1, an embodiment of the present invention isdepicted as an ICD system 10 comprising an implantable electrical pulsegenerating housing 12, an electrical connector pin housing 14, animplantable intravascular discharge catheter 16 electrically connectedto pin housing 14 via a pin connector 18, and an implantableintravascular pacing/sensing catheter 20 electrically connected to pinhousing 14 via a pin connector 22. Discharge catheter 16 carriesproximal defibrillation discharge electrode 24 and distal defibrillationdischarge electrode 26 and is configured to position proximal electrode24 within right atrium 28 and position distal electrode 26 within rightventricle 30. Alternatively, these two electrodes may be on differentcatheters. Pacing/sensing catheter 20, carries two sets ofpacing/sensing electrodes, a proximal electrode set 32 positioned withinthe right atrium 28 and a distal electrode set 34 positioned within theright ventricle 30. Alternatively, electrode sets 32 and 34 may be ondifferent catheters or on the catheter that carries either or bothdefibrillation discharge electrodes 24 and 26. As another alternative,separate electrode pairs may be used for right-ventricular pacing andsensing. The catheters, discharge electrodes and pacing/sensingelectrodes may be of any implantable design known to the art (includingintracardiac, epicardial, intravascular, subcutaneous or submusculardesigns). At least one defibrillation electrode must be intravascular orepicardial, with a preferred embodiment using a pacing electrode anddefibrillation electrode near the right ventricular apex. Positioning ofimplanted pacing electrodes is preferred to be near the rightventricular apex or left ventricle, but is also not critical so long aspacer capture is reliable. This invention also permits determination ofULV without any surface electrodes.

[0097] Because DFTs vary with electrode placement and leadconfiguration, as well as with the responsiveness of a particularpatient's heart, the ULV is determined after the electrodes and leadshave been placed at their permanent positions. In this manner, the DFTcorresponds to the patient and particular arrangement of thedefibrillation electrodes used.

[0098] Referring to FIG. 2, an embodiment of an upper limit ofvulnerability (ULV) subsystem 50 according to the present invention isdepicted in one possible configuration in electrical connection with ashock subsystem 52. ULV subsystem 50 and shock subsystem 52 arecomponent subsystems of ICD 10 of FIG. 1 and are contained withinhousing 12 and electrically connected. ULV subsystem 50 includes atest-shock driver for T-wave shocks 54, a test/treatment controller 56,a timing circuit 58, a sensing, storing, and analyzing circuit 60, apacing circuit 62 (in a preferred embodiment), and a memory unit 64.Shock subsystem 52 may be of any design known to the art, but preferablyis programmable to deliver either monophasic or biphasic shocks, havingvariable tilt, and controllable through a step wise range of energyoutputs from at least 5 J to at least 30 J. Shock subsystem 52 ispreferably connected to the test shock driver 54, memory 64 andcontroller 56 of the ULV subsystem 50. Shock subsystem 52 is used todeliver test shocks as well as defibrillation shocks. The pacing circuit62 is not necessary for embodiments of the method and system which areoperative in a native rhythm.

[0099] The operation of system 10 is described in reference also toFIGS. 3B and 4. System 10 is an embodiment of the invention whichutilizes pacing. The system can be modified to operate in a nativerhythm as described below. Controller 56 is set to test, providing astarting test-shock strength (also called a shock-strength value orenergy level), and triggering sensing circuit 60. This sensing circuitdetects the heart's intrinsic rate and transmits this rate value back tocontroller 56. The starting shock strength is stored in memory unit 64.The intrinsic heart rate value is passed to pacing circuit 62. Pacingcircuit 62 then provides a baseline pacing output through to electrodesets 32, 34 that is of a rate sufficient to overdrive the heart'sintrinsic rate. Referring to FIG. 3B, the sensing, storing, andanalyzing circuit 60 then evaluates the intra-cardiac electrogram 96,which represents the electrical activity of the heart, for the presenceof a QRS complex 92, the derivative of the QRS complex 192, the T-wave94, and the derivative of the T-wave 194.

[0100] The timing of the pacer spike 90 may be transmitted to thesensing circuit electronically by methods well known in the art.Alternatively, the sensing, storing, and analyzing circuit 60 mayidentify the pacer spike 90 during its evaluation of the intra-cardiacelectrogram. The present invention anticipates an ability to evaluatethe ECG or electrogram signals derived from a number of differentconfigurations of implanted electrodes including, but not limited to,intracardiac, epicardial, intravascular, subcutaneous, and submuscularleads. Examples of sensing lead combinations may include leadspositioned to record signals from the superior vena cava, the rightatrium, the right ventricle, the left ventricle and combinations ofelectrodes such as between a lead tip electrode and a defibrillationelectrode or combinations including pairing leads from the right atriumor the superior vena cava to the right or left ventricles.

[0101] Ventricular pacing is performed at a predetermined cycle length,such as 500 ms, for a predetermined duration such as 8-15 beats. Thesensing and storage circuit 60 evaluates the T-waves and their timederivatives from the combinations of implanted electrodes providedduring said ventricular pacing. It uses one of several algorithms forselecting a lead for timing purposes. One such algorithm is to selectthe lead in which the derivative of the T-wave has the latest peak.

[0102] Referring to FIG. 3A, the electrogram was recorded betweenright-ventricular coil and left-pectoral case plus a superior vena cavaelectrode. The timing of the maximum of the derivative of the T-wave(T_(max)) is simultaneous with the peak of the latest-peaking monophasicT-wave on the surface ECG. However, the T-wave 94 of the electrogram(EGM) is biphasic and thus could not be used for analysis by the methodof Chen and Swerdlow (U.S. Pat. No. 5,564,422) referred to in theBackground above. Further, the peak of the T-wave of electrogram EGMoccurs much later than the peak of its derivative. Thus if any ofpreviously-described methods that time shocks relative to the peak ofthe T-wave (referred to in the Background above) were applied to thiselectrogram, they would deliver shocks at incorrect timing intervals.This could result in a significant under-estimate of the ULV andprogramming ICD shock strength to an unsafe value. In contrast, thepresent method selects the peak 98 of the derivative of the T-wave 194for timing purposes.

[0103] In an alternative embodiment of the apparatus of the invention, alead is selected that provides a monophasic T-wave if one is present. Ifthere are multiple leads with monophasic T-waves, it selects the onehaving the latest occurring peak with polarity opposite to that of theQRS complex. If no lead has a monophasic T-wave, it selects the lead inwhich the derivative of the T-wave has the latest peak.

[0104] Referring to FIG. 3B, the base time interval 100 is measuredbetween the pacer spike 90 and the maximum (peak) 98 of the derivativeof the T-wave 194. The test shock is delivered at time 210, offset froma change with respect to time in the T-wave of a cardiac signal (as isalso discussed in the Summary), preferably the maximum of the derivativeof a T-wave, by time ΔT, and corresponding to time interval 200 afterthe pacer spike 90. Offset time (ΔT) is defined in general as thedifference between the time of the test shock (T_(shock)) and the timeof maximum or peak of the relevant cardiac electrical signal (T_(max)).In the preferred embodiments, T_(max) represents either the maximum ofthe time derivative of the T-wave or the peak of the latest-peakingmonophasic T-wave that is opposite in polarity to the QRS complex orsome combination thereof. A negative value of ΔT indicates a timepreceding the peak. A positive value indicates a time after the peak.

[0105] Referring to FIG. 4, the left column indicates determination offour successive base time intervals 100 a-d, corresponding to fourdifferent pacing sequences or trains (a)-(d). The right column indicateshow these base time intervals are used to select the time intervals 200a-d of four successive test shocks at the same shock energy, deliveredrelative to corresponding pacing trains (a′)-(d′), which may be thetrains as (a)-(d) or different trains. Dashed vertical lines in bothcolumns coincide with the maxima 98 a-d of the derivatives of theT-wave. Continuous vertical lines in the right column correspond to theshock time points. In each row, the base time intervals 100 a-d on theleft are added to the corresponding stored values for offset times ΔTa-dto calculate the shock-time intervals 200 a-d, corresponding to testshock times 210 a-d.

[0106] The timing circuit 58 first determines a base time interval 100 ameasured from the pacer spike 90 a to the maximum 98 a of the derivativeof the T-wave 194 a. The base time intervals 100 a-d may be measured onone or more beats preceding the last beat of the same train of pacingpulses as the test shock. Alternatively, it may be measured on animmediately-preceding train of pacing pulses as mentioned previously.These base time intervals may be measured on a single beat or mayrepresent the average of several beats. In one embodiment, pacing trains(a) and (a′) are the same, as are (b) and (b′), (c) and (c′), and (d)and (d′). Then in FIG. 4 each row corresponds to the last two beats ofsuccessive pacing trains (a)-(d). Base time intervals 100 a-d may bemeasured on the next to last beats of the pacing trains (following pacerspikes 90 a-d), and test shocks delivered into the T-wave of the lastbeats of the train (following pacer spikes 90 a′-d′).

[0107] In one embodiment, the baseline time intervals 100 a-d aremeasured on both the preceding pacing train (using either a single-beator average-of-several beats) and on the current pacing train,corresponding to each of the four rows in FIG. 4, using the last beatprior to the test shock. The test shock is aborted if the differencebetween these two measurements is greater than a predetermined value inthe range of 1-40 ms, preferably 5-20 ms, and most preferably 10 ms.This prevents delivery of test shocks in the event that the pacing traindoes not result in consistent capture (due to supraventricular capturebeats, premature ventricular beats, or loss of capture) or the peak ofthe time derivative of the T-wave 194 a-d is not measured consistently.

[0108] The first or starting shock-strength value and a first offsettime (ΔTa) are stored in memory unit 64 and are transmitted totest-shock driver 54. The test-shock driver 54 triggers shock subsystem52 to deliver a first test shock with the starting shock strength at afirst shock time point 210 a, which occurs at first time interval 200 aafter the next pacing spike 90 a′. First time interval 200 a, determinedby timing circuit 58, is calculated by adding the first offset time ΔTato the previously measured base time interval 100 a. In FIG. 5 T_(max)refers to the maxima 98 a-d of the derivatives of the T-waves 194 a-d.In an alternative embodiment, it may refer to the peak of a monophasicT-wave.

[0109] Note that the base time interval 100 shortens between pacingtrains (b) and (d), but the offset times ΔT_(a-d) remain fixed relativeto the maxima of the derivatives 98 a-d.

[0110] The starting shock strength and offset time ΔTa-d are stored inmemory unit 64 and are chosen according to a predetermined protocol. Thestarting shock strength is in the range of 5-30 J, preferably between10-15 J, and most preferably 15 J. Offset time ΔT may be positive,negative or zero. Offset time ranges between negative (−) 60 ms andpositive (+) 40 ms and is preferably −20 ms to +40 ms for a standardthree-electrode defibrillation configuration (right-ventricle to caseplus superior vena cava). At least one offset time is stored andpreferably four (4) in the preferred embodiment. The initial value ofoffset time ΔT is preferably about 0 ms whereby the initial test shockis delivered such that it substantially coincides with the maximum ofthe derivative of the T-wave following the next pacer spike 90 a′.

[0111] In an alternative normal-rhythm embodiment of the apparatus, timedelays are calculated in a similar fashion, except that they are basedon measurements made in normal rhythm. A time interval is calculatedbased on the interval between the detected QRS complex (as opposed to apacer spike) and the peak of the time derivative of the selectedintra-cardiac T-wave.

[0112] In most cases, the initial test shock energy is sufficientlystrong such that fibrillation is not induced. After delivery of thefirst test shock, pacing from the pacing circuit 62 is turned off andthe cardiac rhythm is monitored by the sensing and storage circuit 60for the presence of fibrillation.

[0113] If fibrillation is not induced by the first test shock,controller 56 waits a predetermined period of time, preferably about one(1) minute, before starting the next test shock. During this and allsubsequent waiting periods, a pacing train (in this case train (b)) maybe delivered and analyzed by sensing and storage circuit 60. Thisanalysis updates interval 100 based on the timing of the maximum of thederivative of the intra-cardiac T-wave. This updated interval 100 isstored in timing circuit 58 for the next test-shock pacing sequence.Alternatively, sensing and storage circuit 60 may analyze the timing ofthe maximum of the derivative of the intra-cardiac T-wave during thepaced beats of each pacing train and that value may be used to determinethe timing of the shock at the end of the same pacing train. In thiscase, no pacing train is delivered during the waiting period, and thevalue of interval 100 is not updated until the waiting period ends andthe test-shock's pacing train begins. In either case, these additionalmeasurements result in updated measurements 100 b-d of the base timeinterval 100 for each successive test shock in the sequence as shown inFIG. 4.

[0114] After the first test shock and monitoring and waiting period,controller 56, is programmed to deliver up to three additional sequences(a total of four) of ventricular pacing at a predetermined cycle lengthfor a predetermined number of beats followed by test shocks at the samestarting shock strength (a total of four test shocks), at differentintervals 200 b-d corresponding to times 210 b-d, followed by additionalmonitoring and waiting periods.

[0115] For the second test shock in the first round of test shocks,timing circuit 58 determines a second time interval 200 b from the pacerspike 90 b, corresponding to the base time interval 100 b plus a secondΔTb 210 b which is preferably plus 20 ms. The heart is shocked at theend of this interval 200 b, which occurs at second shock time point 200b, which falls 20 ms after the maximum derivative 98 b of the T-wave 194b.

[0116] If fibrillation is not induced, the controller 56 waits thepredetermined wait period before initializing the chain of eventsleading to the third test shock at the first shock strength andcommences with timing circuit 58 determining a third time interval 200 cfrom pacer spike 90 c corresponding to base time interval 100 c plusthird ΔTc which is preferably minus 20 ms. The heart is shocked at theend of this interval 200 c, which occurs at third time point 210 c whichis preferably 20 ms before maximum derivative 98 c of the T-wave 194 cand the heart is shocked again.

[0117] If fibrillation is not induced by the third test shock, thecontroller 56 waits the predetermined wait period before initializingthe chain of events that results in a fourth test shock at the firstshock strength. Timing circuit 58 determines a time interval 200 d frompacing spike 90 d corresponding to the base interval 100 plus a fourthΔTd which is preferably plus 40 ms. The resultant shock time point 210 dthat is preferably 40 ms after the maximum 98 d derivative of the T-wave194 d. After each test shock the cardiac rhythm is monitored by thesensing circuit 60 to ascertain if the shock has induced fibrillation.If fibrillation is not induced, the controller 56 waits thepredetermined wait period before delivering the next test shock.

[0118] In the example shown in FIG. 4, base time interval 100 shortensbetween the times of the second and third rows so that base intervals100 c and 100 d are shorter than base intervals 100 a and 100 b.Similarly, shock timing intervals 200 c and 200 d are shorter than shocktiming intervals 200 a and 200 b. However, the offset intervals ΔTc andΔTd remain appropriately timed relative to the peaks of theircorresponding derivatives 194 c and 194 d. Although this illustrationshows only one change in base time interval 100, any change in this basetime interval is accompanied by a corresponding change in the shock-timeinterval 200.

[0119] If fibrillation is not induced by a series of four T-wave shocksat the same shock strength shock and different intervals 200 a-d,controller 56 lowers the shock strength by a predetermined test-shockstrength decrement value which is also stored in memory unit 64 and setby a predetermined protocol. The controller 56 waits the predeterminedwait period before transmitting the newly determined, second test-shockstrength to the test-shock driver 54 and then to shock subsystem 52after the predetermined waiting period. This initiates a second seriesof up to four test shocks. The first test shock in the second round isdelivered at a first time point corresponding to a first timing intervaldetermined by timing circuit 58 after a pacing spike 90. Preferably, allof the time offsets ΔT in the second round are equivalent to those inthe first test shock sequence. However, one or more of the time offsetsmay be varied. The amount by which the second test-shock strength isreduced relative to the first shock strength (i.e. the shock energydecrement value) is in the range of 1-10 J, usually in the range of 2-5J. The preferred decrement value is about 5 J at test-shock strengths of10 J or greater and about 2 J at test-shock strengths of about 5 J orless. The specific values may be selected from one of various testingstrategies, including those used for selecting shock decrement valuesfor DFT testing. The sequence of test shocks in the second sequence isrepeated in the same manner as that described with respect to thestarting sequence until fibrillation is induced.

[0120] If fibrillation has not been induced after the second round oftest shocks, one or more subsequent rounds of test shocks may beadministered until the system minimum level shock strength, typically 2J-5 J, is reached. Each subsequent round preferably has the same maximumnumber of test shocks, each delivered at the same corresponding timeoffsets ΔT relative to the end of time interval 100, which is updatedprior to each test shock. The test-shock strength of the next round isdetermined by lowering the shock strength of the previous round by adecrement value that in general is specific to the shock valuecorresponding to the previous round. Therefore, in this embodiment, foreach test-shock strength, there is a set of up to four test-shocks,corresponding to each of the four shock time points 210 a-d, calculatedby adding an offset times ΔTa-d to base time intervals 100 a-d. In apreferred embodiment, time intervals 200 a-d are calculated based onelectrogram measurements made in paced rhythm.

[0121] If a test shock in any shock sequence induces fibrillation thenthe shock strength of the last shock sequence in which no shock inducedfibrillation (i.e. the shock strength of the prior shock sequence) maybe accepted as the step-down ULV (which is an accurate estimate of theDFT). If fibrillation has not been induced even at the system minimum,1-5 J level as determined in step 85, the ULV is calculated to be theminimum tested shock strength in step 87; and the defibrillation shockstrength is set to a level incrementally above the ULV, preferably withan increment of at least 5 J.

[0122] In the safety-margin embodiment referred to previously, testingis limited to the first round or sequence of four shocks at a singleshock strength if fibrillation is not induced. No second or subsequentround is utilized. The first ICD shock is then programmed incrementallyabove this value.

[0123] As was discussed above, in most cases the initial test shockenergy is sufficiently strong such that fibrillation is not induced. Thepresent invention anticipates that a small fraction of patients willfibrillate in response to the first shock strength. Referring to FIG. 5,this condition is identified in step 89. If this occurs, the test-shockstrength is incremented to a next higher shock strength in step 70 basedon data stored in memory 72 and testing is repeated. As noted above,this testing consists of pacing the heart for a predetermined number ofbeats, delivering a shock at a predetermined time interval after thelast pacer spike, observing for the induction of fibrillation, and iffibrillation is not induced iterating this process at up to three othertime intervals. If fibrillation is not induced by any shock at thishigher shock strength, step 89 a determines that fibrillation has beeninduced at least once. Step 89 b then determines if the present shock isthe last shock in a four-shock sequence. If it is, the ULV is set equalto this value in step 87. If the present shock is not the last shock ina four-shock sequence, step 89 b continues the testing sequence.

[0124] If fibrillation is induced, step 85 b again determines if thepresent shock value equals the system maximum shock strength. If it doesnot, waiting period 83 is reinitiated, counter 84 is reset to 1, and theshock strength is incremented to the next higher value in step 70 basedon data stored in memory 72. The testing process is iterated until ashock strength is reached at which fibrillation is not induced by any offour test shocks as determined by step 89 b. This shock strength is setequal to the ULV in step 87. If test shocks at the maximum system energyinduce fibrillation, the ULV is determined to be greater than this valuein step 88 b. In this case, the ICD system usually is revised bychanging electrodes, shock waveform or polarity, maximum system energy,or some other parameter.

[0125] Alternative embodiments may provide more accurate estimates of ashock strength associated with a specific probability of defibrillationsuccess, but they require additional fibrillation-defibrillationepisodes. These involve the concept of multiple reversals between shockstrength that do not induce fibrillation and those that do inducefibrillation analogous to the reversal of response methods fordetermining the DFT. Methods that utilize a specific number ofequal-size reversal steps or a Bayesian method for selecting unequalsteps can be applied to ULV testing as well as to DFT testing. Theyprovide a more accurate estimate of a specific point of thedefibrillation probability of success curve.

[0126] In one embodiment, the baseline time intervals 100 a-d aremeasured on both the preceding pacing train (using either a single-beator average-of-several beats) and on the current pacing train,corresponding to each of the four rows in FIG. 5, using the last beatprior to the test shock. The test shock is aborted if the differencebetween these two measurements is greater than a predetermined value inthe range of 1-40 ms, preferably 5-20 ms, and most preferably 10 ms.This prevents delivery of test shocks in the event that the pacing traindoes not result in consistent capture (due to supraventricular capturebeats, premature ventricular beats, loss of capture) or the peak of thetime derivative of the T-wave 194 a-d is not measured consistently.

[0127] While the above embodiments are implemented in an ICD, theinvention can also be implemented in an ICD programmer or an independentexternal device for testing defibrillation efficacy. Such a device maybe referred to as “an implant-support device.”

[0128] When the invention is implemented in a programmer orimplant-support device, surface ECG leads, one or more electrogramsincluding the electrogram that is differentiated, and the differentiatedsignal may be displayed on a computer screen to be viewed by anoperator. The timing points 90 a-d, and 98 a-d and timing intervals 100a-d may also be displayed on the computer screen. In one embodiment testshocks are not delivered unless the operator confirms theautomatically-selected timing points and intervals. The operator mayalter the timing points and intervals manually using an input devicesuch as a mouse, trackball, touch-screen pen, or other such inputdevices that are well known in the art. This operator-assisted method ofselecting timing points and intervals may also be used with an ICD. Inthis embodiment, the electrograms, differentiated electrograms, timingpoints and timing intervals are sent from the ICD to the programmer viatelemetry, and the programmer telemeters the confirmation signal ormodifications of the timing points and intervals to the ICD prior todelivery of the test shock. In these operator-assisted embodiments, thebaseline time intervals 100 a-d are measured on one preceding pacingtrain and the test shocks are delivered on a subsequent pacing train.

[0129] Referring also to FIG. 5, a preferred embodiment of the method ofthe present invention begins with step 72 wherein a first or startingtest-shock strength, one or more offset time intervals (ΔT), and one ormore test-shock strength decrement value(s) are stored in and retrievedfrom memory unit 64 of the ULV subsystem 50. The starting shockstrength, shock decrement value, and offset times ΔT are chosenaccording to a predetermined protocol. As was discussed above withrespect to the apparatus of the invention, the preferred first shockstrength is in the range of 10-15 J, but may range from 5 J to 30 J. Thepreferred number of shocks is four (4). Therefore, in this embodiment,for each test-shock strength there is a set of up to four test shockscorresponding to each of the four shock time points 210 a-d. Eachtest-shock time 210 a-d, falls at the end of time intervals 200 a-d,after a respective pacing spikes 90 a-d′. The time intervals 210 a-d,210 b, 210 c and 210 d are calculated by adding an offset times ΔTa-d tobase time intervals 100 a-d. The base time 100 a-d is the time betweenthe pacing spike 90 a-d to the maximum derivative of the T-wave 194 a-din the electrogram 192 a-d proceeding electrograms 192 a-d. In apreferred embodiment of the invention, time intervals 200 a-d arecalculated based on electrogram measurements made in paced rhythm.

[0130] However, these shock-time intervals may alternatively be based onmeasurements made in normal rhythm as described below. In the preferredembodiment, step 74 initiates overdrive pacing of the heart. One methodfor selecting intervals in paced rhythm is shown in step 73. This methodmay be applied only if a recorded electrogram has a suitable monophasicT-wave.

[0131] In step 76, pacing is confirmed and electrograms are recorded. Instep 73, the peak of the latest peaking monophasic T-wave is identifiedby analyzing electrogram morphology in each recorded lead. The preferredmethod for selecting intervals in paced rhythm is shown in steps 71, 75,and 77. This method can be applied regardless of whether a monophasicT-wave is present. In step 71, the electrograms recorded and analyzed instep 76 are differentiated with respect to time. In step 75, the maximumof the time derivative of the T-wave is determined from the first timederivative of each electrogram 196 a, the latest of these peaks 98 a isselected, and base time 100 a is calculated from the pacer spike 90 a tosuch peak 98 a. In step 78, a shock-time interval 200 a is calculated byadding one of a predetermined time offset intervals ΔT stored in step 72to the base interval 100 a determined in step 75. ΔT may be positive,negative, or zero. Offset time ΔT ranges between negative (−) 60 ms andpositive (+) 40 ms and is preferably −40 ms to +20 ms. The initial ΔTaispreferably about 0 ms. In the preferred embodiment, first time interval200 a is calculated based on ΔTa of 0 ms. It starts at the time ofpacing spike 90 a′ and ends at shock-time point 210 a, which occurssubstantially simultaneously with the latest maximum peak of thederivative of the T-wave. As FIG. 3A shows, it is also substantiallysimultaneous with the peak of the latest-peaking monophasic T-wave onthe surface ECG. In subsequent cycles of step 78, where applicable,second, third and fourth intervals may be calculated. Second timeinterval 200 b is based on ΔTb of +20 ms and begins at pacer spike 90 band yields shock time point 210 b which is approximately 20 ms after themaximum 98 b of the derivative of the T-wave 194 b. Third time interval200 c is based on ΔTc of −20 ms, begins at pacer spike 90 c and yieldsthird time point 210 c which is about 20 ms before the maximum 98 c ofthe derivative of the T-wave 194 c. The fourth interval 200 d is basedon ΔTd of +40 ms, begins at pacer spike 90 d and yields fourth shocktime point 210 d which is about 40 ms after the maximum 98 d of thederivative of the T-wave 194 d.

[0132] Then after the next suitable pacer spike 90 a′, step 80 initiatesa first test shock which is delivered to the heart after first interval200 a calculated in step 78. Following first test shock, pacing isturned off in the embodiment utilizing pacing, and the heart ismonitored for the induction of fibrillation at step 82. As was discussedabove in connection with the apparatus of the invention, in most cases,the initial test shock energy is sufficiently high such thatfibrillation is not induced. If no fibrillation is detected, step 83involves waiting a predetermined period of time of approximately one (1)minute, and a counter is incremented at step 84. Subsequently, theprocess is repeated beginning at selection step 70 selecting the nextoffset time T and utilizing the same (first) shock strength. The processmay be repeated up to a predetermined maximum number of shocks,preferably four (4), in a round or sequence, at the first test-shockstrength. Since the first shock strength is selected such that it is toohigh to induce fibrillation in most patients, usually a second sequenceor round of one or more test shocks up to the predetermined maximumnumber per round will be initiated, at preferably the same shock-timedelays, but at a lower shock strength.

[0133] After the first sequence of a preselected number of test shocksat the same energy, the counter has reached the predetermined maximum,in this case four. Then step 84 resets the counter to one. This causesstep 70 to determine a new test-shock strength based on adding thepredetermined shock decrement value stored in step 72, preferably 5 J,to the existing test-shock strength used in step 70. The second round orsequence of test shocks then delivers shocks in the same manner as thatdescribed above with respect to the first sequence. If after the secondround of test shocks, fibrillation has not been induced, one or moreadditional rounds of test shocks are administered provided the systemminimum level of shock strength, typically 5 J, has not been reached asdetermined in step 85. Each subsequent round utilizes a lower shockstrength from that value used in the previous round at step 70 based onthe shock decrement value. If fibrillation has not been induced even atthe system minimum, 5 J level as determined in step 85, the ULV iscalculated to be equivalent to 5 J in step 87, and the defibrillationshock strength is set to a level incrementally above the ULV.

[0134] In an alternative normal rhythm embodiment of the method, timedelays are calculated in a similar fashion, except that they are basedon measurements made in normal rhythm or atrial-paced rhythm. A timeinterval is calculated based on the interval between the detected QRScomplex (as opposed to a pacer spike) and the peak of the timederivative of the selected intra-cardiac T-wave. In the alternativenormal rhythm embodiment, step 76 also includes the sub-step ofdetermining that the heart's rhythm is sufficiently regular that thetime interval between the detected QRS complex and the peak of thederivative of the intra-cardiac T-wave is likely to be substantiallyconstant over a few beats.

[0135] The principal advantage of the present invention is the capacityto automate determination of the optimal first shock strength fortransvenous ICDs using only implanted electrodes by determining the ULVwith improved accuracy, safety, speed and simplicity. The presentinvention is substantially improved over previous methods of determiningthe ULV for purposes of predicting the DFT and is of sufficient accuracythat conventional DFT testing is unnecessary. The time required for theprocedure is substantially shortened by diminishing the number ofepisodes of fibrillation, the number of shocks in regular rhythm, theneed to record a 12-lead surface ECG, and the need to make cumbersomemeasurements from the 12-lead surface ECG. The present invention is easyto apply because all measurements can be automated in the software ofthe ICD or programmer.

[0136]FIG. 6 is a graph that compares the timing of the peak of thelatest peaking monophasic T-wave on the surface ECG with the timing ofthe maximum derivative of the T-wave determined from ICD electrodes. Theordinate shows the timing difference (in ms) between the peak of thelatest-peaking T-wave on the surface ECG and timing of the maximumderivative of the T-wave recorded from totally-implanted ICD electrodes.The abscissa represents 25 consecutive patients studied at ICD implant.The electrogram is recorded from either a two-electrode shockingconfiguration (right-ventricular coil to left-pectoral case) or athree-electrode shocking configuration (right-ventricular coil toleft-pectoral case plus a superior vena cava electrode). The meandifference was 2 ms with a standard deviation of 11 ms. The maximumabsolute difference for an individual-patient was 23 ms.

[0137]FIG. 7. shows the timing of the most vulnerable intervals,representing the peak of the vulnerable zone, in relation to the timingof the maximum derivative of the T-wave (corresponding to time 0)determined from the same 25 patients shown in FIG. 6. The range of −20to +40 ms relative to the maximum derivative of the T-wave includes thepeak of vulnerable zone in 24 patients (96%). For Patient 1, the peak ofthe vulnerable zone precedes the maximum derivative of the T-wave by 29ms. Note that the peak of the vulnerable zone is relatively narrow withboth mean and median width of 20 ms. It includes only one two 20-msintervals in 80% of patients. Thus, if only one or two T-wave shocks aregiven (as recommended in previous methods discussed in Backgroundsection), small errors in their T-wave shocks can result in erroneousmeasurement of the ULV.

[0138] The descriptions above and the accompanying drawings should beinterpreted in the illustrative and not the limited sense. While theinvention has been disclosed in connection with an embodiment orembodiments thereof, it should be understood that there may be otherembodiments which fall within the scope of the invention as defined bythe claims. Where a claim, if any, is expressed as a means or step forperforming a specified function it is intended that such claim beconstrued to cover the corresponding structure, material, or actsdescribed in the specification and equivalents thereof, including bothstructural equivalents and equivalent structures, material-basedequivalents and equivalent materials, and act-based equivalents andequivalent acts.

What is claimed is:
 1. A method for determining a cardiac shockstrength, comprising the steps of: (a) sensing a change with respect totime in a T-wave of an electrical cardiac signal; (b) delivering a testshock by: (i) delivering a test shock at a test-shock strength and at atest-shock time relating to sensing the change with respect to time inthe T-wave; and (ii) sensing for cardiac fibrillation; and (c) iffibrillation is not sensed, repeating step (b) at the test-shockstrength and at a different test-shock time relating to the change inthe T-wave; and (d) if fibrillation is sensed, setting the cardiac shockstrength as a function of the test-shock strength.
 2. The method ofclaim 1, wherein the change with respect to time is a change inamplitude.
 3. The method of claim 1, wherein the change with respect totime is selected from the group consisting of a finite difference, anordinary derivative, a directional derivative, a gradient, a partialderivative, an implicit differential, a variance calculation, a boundedvariation calculation, a radial displacement vector, and a tangentvector approximation.
 4. The method of claim 1, wherein the change withrespect to time is an extreme value calculated by a method selected fromthe group consisting of a finite difference, an ordinary derivative, adirectional derivative, a gradient, a partial derivative, an implicitdifferential, a variance calculation, a bounded variation calculation, aradial displacement vector, and a tangent vector approximation.
 5. Themethod of claim 1, wherein the change with respect to time is a maximalvalue calculated by a method selected from the group consisting of afinite difference, an ordinary derivative, a directional derivative, agradient, a partial derivative, an implicit differential, a variancecalculation, a bounded variation calculation, a radial displacementvector, and a tangent vector approximation.
 6. The method of claims 2-5,wherein the change with respect to time is a derivative of T-waveamplitude with respect to time.
 7. The method of claims 2-5, wherein thechange with respect to time is a derivative of T-wave amplitude withrespect to time selected from the group consisting of the firstderivative, second derivative, third derivative, and nth derivative. 8.The method of claim 7, wherein the change with respect to time is thefirst derivative of T-wave amplitude with respect to time.
 9. The methodof claim 1 in which test-shock times are selected in relation to themaximum of the first derivative of the T-wave with respect to time. 10.The method of claim 1, wherein step (b) is performed in native rhythm ofthe heart, and wherein the test-shock time is further based on a sensedQRS complex of the cardiac signal.
 11. The method of claim 1, whereinstep (b) is performed in atrial-paced rhythm of the heart, and whereinthe test-shock time is further based on a sensed QRS complex of thecardiac signal.
 12. The method of claim 1, wherein step (b) is performedin ventricular-paced rhythm of the heart, and wherein the test-shocktime is further based on a pacer spike.
 13. The method of claim 1,wherein step (b) is performed in atrioventricular-paced rhythm of theheart, and wherein the test-shock time is further based on a ventricularpacer spike.
 14. The method of claim 1, wherein the test-shock time isrecalculated in accordance with step (a) and (b)(i) if fibrillation isnot sensed.
 15. The method of claim 1, wherein each test-shock time ispredetermined.
 16. The method of claim 1, wherein step (b) is repeatablea maximum number of times, and wherein if fibrillation is not sensed atthe maximum number, a therapeutic cardiac shock strength is set as avalue greater then the test-shock strength.
 17. The method of claim 1,wherein step (b) is repeatable a maximum number of sequence times, andwherein if fibrillation is not sensed at the maximum number, thetest-shock strength is changed by an amount and steps b-c are repeatedin a new sequence.
 18. The method of claim 17, wherein the changedamount is based on at least one of the outcomes from a previous sequenceof test shocks.
 19. The method of claim 17, wherein the changed amountis determined using a method based on at least one of the outcomes fromthe previous sequence of test shocks.
 20. The method of claim 17,wherein the changed amount is determined using a method based on atleast one of the outcomes from the previous sequence of test shocks andtaken from the group of methods consisting of including “up-down” andBayesian methods.
 21. The method of claim 20, wherein, if fibrillationis not sensed at a predetermined minimum shock strength, furthercomprising the step of setting the cardiac shock strength at thepredetermined minimum shock strength.
 22. The method of claim 17,wherein the changed amount is increased.
 23. The method of claim 17,wherein the changed amount is a function of the test-shock strength. 24.The method of claim 17, wherein the changed amount is a predeterminedvalue.
 25. The method of claim 1, wherein the cardiac shock strength isa function of the lowest test-shock strength that does not inducefibrillation.
 26. The method of claim 25, wherein the function is 5 Jmore than the lowest test-shock strength that does not inducefibrillation.
 27. A method for determining a cardiac shock strength fora medical device connected to a patient and capable of delivering ashock, comprising the steps of: (a) delivering a set of test shocks withthe device to the patient, each member of the set comprising the substeps of: (i) sensing an electrogram from the patient; (ii) detectingthe maximum derivative of a T-wave of the electrogram; (iii) deliveringa test shock to the patient at a test-shock strength and at a test-shocktime relating to the maximum derivative of the T-wave; (iv) sensing forinduction of cardiac fibrillation; and (v) if fibrillation is not sensedin step a(iv), then repeating sub-steps a(i-iv) at the test-shockstrength up to a predetermined maximum set number, each member of theset having a different test-shock time relating to the maximumderivative of the T-wave; and (b) if fibrillation is not sensed in step(a) after the maximum set number, then repeating step (a) at a lowertest-shock strength; and (c) if fibrillation is sensed in step (a), thendefibrillating the patient and setting the cardiac shock strength as apredetermined function of the test-shock strength that inducedfibrillation.
 28. A method for determining an optimal programmedfirst-shock strength of an implantable cardioverter defibrillator,comprising the steps of: (a) delivering a set of test shocks having apredetermined maximum number of members with the cardioverterdefibrillator to the patient, each member of the set comprising the substeps of: (i) sensing an electrogram from the patient; (ii)differentiating the electrogram; (iii) detecting the maximum of thederivative with respect to time of a T-wave of an electrogram; (iv)delivering a test shock to the patient at a test-shock strength and at atest-shock time relating to the maximum of the derivative with respectto time of the T-wave; (v) sensing for an induction of cardiacfibrillation; and (vi) if fibrillation is not sensed in step a(v), thenrepeating sub steps a(i-v) at the same test-shock strength up to apredetermined maximum set number, each member of the set having adifferent test-shock time relating to the maximum of the derivative ofthe T-wave with respect to time; and (b) if fibrillation is not sensedin step (a) after the maximum set number, then repeating step (a) at alower test-shock strength; and (c) if fibrillation is sensed in step(a), then defibrillating the patient and setting the programmedfirst-shock strength of an ICD at a predetermined higher level than thetest-shock strength that induced fibrillation.
 29. A method fordetermining an optimal programmed first-shock strength of an implantablecardioverter defibrillator, comprising the steps of: (a) delivering aset of up to five test shocks with the cardioverter defibrillator to thepatient, each test shock member of the set of test shocks comprising thesub steps of: (i) sensing an electrogram from the patient; (ii)differentiating the electrogram; (iii) detecting the maximum of thefirst derivative with respect to time of a T-wave of an electrogram;(iv) delivering a test shock to the patient at a test-shock strength andat a test-shock time relating to the maximum of the first derivative ofthe T-wave with respect to time; (v) sensing for an induction of cardiacfibrillation; and (vi) if fibrillation is not sensed in step a(v), thenrepeating sub steps a(i-v) at the same test-shock strength up to andincluding the last of up to five test shocks, each test shock member ofthe set of test shocks having a different test-shock time relating tothe maximum of the first derivative of the T-wave with respect to time;and (b) if fibrillation is not sensed in step (a) by the last of up tofive test shocks, then repeating step (a) at a lower test-shockstrength, to deliver at least one additional set of up to five testshocks; and (c) if fibrillation is sensed in step (a), then: (i)defibrillating the patient with the implantable cardioverterdefibrillator; and (ii) setting the optimal programmed first-shockstrength of an ICD of the implantable cardioverter defibrillator at apredetermined higher level than the test-shock strength at whichfibrillation was induced.
 30. A method for determining an optimalprogrammed first-shock strength of a first therapeutic shock of animplanted cardioverter defibrillator relative to the upper limit ofvulnerability, the implanted cardioverter defibrillator having at leastone sensing electrode and at least one shocking electrode, comprisingthe steps of: (a) setting an initial test-shock strength, four offsettimes, and a shock strength decrement; (b) delivering a set of up tofour test shocks with the implantable cardioverter defibrillator to thepatient, each test shock member of the set of test shocks comprising thesub steps of: (i) sensing an electrogram from the patient; (ii)detecting at least one predetermined base timing point prior to theT-wave of the electrogram; (iii) differentiating the electrogram withrespect to time; (iv) detecting at least one maximum of the firstderivative with respect to time of a T-wave of the differentiatedelectrogram; (v) measuring at least one base time interval from the atleast one base timing point to the at least one maximum of the firstderivative with respect to time of a T-wave; (vi) delivering a testshock to the patient at the test-shock strength and at a test-shock timecorresponding to the base time interval plus one of the offset times;(vii) sensing for an induction of cardiac fibrillation for apredetermined sensing time period; and (viii) if fibrillation is notsensed in step b(vii), then repeating sub steps b(i-vii), at the sametest-shock strength, up to the fourth test shock, each test shock memberof the set of test shocks having a different test-shock timecorresponding to a base time interval plus an offset time; and (c) iffibrillation is not sensed in step (b) by the fourth test shock, thenrepeating step (b) at a lower test-shock strength corresponding to theshock strength decrement, to deliver at least one additional set of upto four test shocks; and (d) if fibrillation is sensed in step (b),then: (i) defibrillating the patient; and (ii) setting the programmedfirst-shock strength of the implantable cardioverter defibrillator at apredetermined higher level than the weakest test-shock strength at whichfibrillation was not induced, which test-shock strength represents theupper limit of vulnerability.
 31. The method of claim 30, furthercomprising the step, after step (d), of repeating steps (c) and (d) aspecified number of times.
 32. The method of claim 30, wherein thesensing and detecting steps are implemented entirely with signalsobtained from implanted electrodes.
 33. The method of claim 32, whereinat least one implanted electrode is an intracardiac electrode.
 34. Themethod of claim 32, wherein at least one implanted electrode is anintravascular electrode.
 35. The method of claim 32, wherein at leastone implanted electrode is a subcutaneous electrode.
 36. The method ofclaim 32, wherein at least one implanted electrode is a submuscularelectrode.
 37. The method of claim 32, wherein at least one implantedelectrode is an epicardial electrode.
 38. The method of claim 30,wherein at least one electrode is externally disposed.
 39. The method ofclaim 30, wherein the initial shock strength is a sufficientlyphysiologically high energy value that it is not likely to causefibrillation.
 40. The method of claim 30, wherein the initial shockstrength is in the range of 5-30 J.
 41. The method of claim 30, whereinthe initial shock strength is in the range of 10-15 J.
 42. The method ofclaim 41, wherein the initial shock strength is 15 J.
 43. The method ofclaim 30, wherein (a) the implantable cardioverter defibrillatortelemeters to a programmer i) a plurality of electrograms, ii) thedifferentiated electrogram, iii) the base timing point determined inclaim 30 (b) (ii), iv) the timing point determined by maximum of thederivative of a T-wave claim 30 (b) (iv), and v) the base time intervalin claim 30 (b) (v), (b) the programmer displays on a computer screen aplurality of one or more surface ECG leads and one or more signals takenfrom electrograms, differentiated electrograms, and timing points andtiming intervals telemetered from the implantable cardioverterdefibrillator; and (c) an operator views the screen; and (d) if theoperator confirms the timing of timing points indicated in (a) (iii) and(a) (iv) of the present claim using a programmer-input device (such as amouse, trackball, or touch-screen pen), the implantable cardioverterdefibrillator delivers the test shock in claim 30 (b) (vi); and (e) ifthe operator does not confirm the timing of timing points indicated in(a) (iii) and (a) (iv) of the present claim, the operator adjusts thetiming of one of these points on the programmer (using a computer inputdevice such as a mouse, trackball, or touch-screen pen), and (f) theprogrammer transmits the adjusted values of these timing points viatelemetry to the implantable cardioverter defibrillator, and (g) theimplantable cardioverter defibrillator uses these adjusted timing pointsto calculate adjusted base time interval and test-shock timecorresponding to the adjusted base time interval plus one of the offsettimes; and (h) the implantable cardioverter defibrillator delivers thetest shock in claim 30 (b) (vi) at the adjusted test-shock time.
 44. Themethod of claim 30, wherein the number of T-wave shocks and theircorresponding offset times are functions of both the location of pacingelectrode and the configuration of the electrodes used fordefibrillation.
 45. The method of claim 30, wherein the offset times areless than one half the time duration of the T-wave.
 46. The method ofclaim 30, wherein the offset times are less than 100 millisecondsabsolute value.
 47. The method of claim 46, wherein the offset times areless than 50 milliseconds absolute value.
 48. The method of claim 46,wherein the offset times are less than or equal to 40 millisecondsabsolute value.
 49. The method of claim 46, wherein the offset times arebetween 0 and 40 milliseconds absolute value.
 50. The method of claim49, wherein at least one offset time is a positive value, to thereby beadapted to deliver a test shock after the maximum of the firstderivative of the T-wave with respect to time.
 51. The method of claim49, where in at least one offset time is a negative value, to thereby beadapted to deliver a test shock before the maximum of the firstderivative of the T-wave with respect to time.
 52. The method of claim49, wherein one offset time is 0, to thereby be adapted to deliver atest shock substantially at the maximum of the first derivative of theT-wave with respect to time.
 53. The method of claim 49, wherein atleast one offset time is negative and at least one offset time ispositive, to thereby be adapted to deliver at least one test shock afterthe maximum of the first derivative of the T-wave with respect to timeand at least one test shock before the maximum of the first derivativeof the T-wave with respect to time.
 54. The method of claim 49, whereina first offset time is 0, a second offset time is −20 milliseconds, athird offset time is −40 milliseconds, and a fourth offset time is +20milliseconds.
 55. The method of claim 49, wherein a first offset time is0, a second offset time is +20 milliseconds, a third offset time is −20milliseconds, and a fourth offset time is +40 milliseconds.
 56. Themethod of claim 49, wherein there are three test shocks with a firstoffset time of 0, a second offset time of +20 milliseconds a thirdoffset time of −20 milliseconds.
 57. The method of claim 30, wherein theoffset time in a set are constant.
 58. The method of claim 30, whereinthe offset time in a set are variable
 59. The method of claim 58,further comprising the step of adjusting the offset time within a set.60. The method of claim 30, wherein the offset time in each set areidentical to offset-times in other sets.
 61. The method of claim 30,wherein the offset time in at least one set vary relative to offset timein at least one other set.
 62. The method of claim 61, furthercomprising the step of adjusting the offset time of at least one steprelative to the offset time of at least one other step.
 63. The methodof claim 30, wherein the shock strength decrement is in a range of 1-10J.
 64. The method of claim 63, wherein the shock strength decrement isin a range of 2-5 J.
 65. The method of claim 64, wherein the shockstrength decrement is 5 Joules.
 66. The method of claim 30, wherein theshock strength decrement is a constant value.
 67. The method of claim30, wherein the shock strength decrement is a variable value.
 68. Themethod of claim 67, wherein the shock strength decrement is about 5 Jfor test-shock strengths of greater than or equal to 10 J, and whereinthe shock strength decrement is about 2 J for test-shock strengths ofless than or equal to 5 J.
 69. The method of claim 30, wherein thepredetermined sensing time period of step (b) (vii) is 1-10 seconds. 70.The method of claim 30, wherein a waiting period is initiated after thesensing period of step (b)(vii) and prior to repeating sub stepsb(i-vii) at the same shock strength.
 71. The method of claim 70, whereinthe waiting period is about 1 minute.
 72. The method of claim 30,wherein a waiting period is initiated after the sensing period of step(b) (vii) and prior to repeating sub step 18(b) at a lower shockstrength.
 73. The method of claim 72, wherein the waiting period isabout 1 minute.
 74. The method of claim 30, wherein step (d) furthercomprises the sub-step of storing the shock value, plus the shockdecrement value in the memory of the device as the defibrillationthreshold energy.
 75. The method of claim 30, wherein step (b) isaccomplished when the heart is in its native rhythm and wherein the basetiming point is chosen in relation to timing of the QRS complex.
 76. Themethod of claim 75, wherein the base timing point is the minimum timederivative of the QRS complex.
 77. The method of claim 75, wherein thebase timing point is the maximum or minimum time derivative with thegreatest absolute value of the QRS complex.
 78. The method of claim 75,wherein the base timing point is the maximum time derivative of the QRScomplex.
 79. The method of claim 75, wherein the base timing point isthe maximum value of the QRS complex.
 80. The method of claim 75,wherein the base timing point is the minimum value of the QRS complex.81. The method of claim 75, wherein the base timing point is the maximumor minimum of greatest absolute value of the QRS complex.
 82. The methodof claim 30, wherein step (b) is accomplished when the heart is in itspaced rhythm, further comprising the step, performed before step (b)(i),of pacing the heart and wherein the base timing point is chosen inrelation to the timing of the pacer spike.
 83. The method of claim 82,wherein the base timing point is the pacer spike.
 84. The method ofclaim 82, wherein the heart is paced at a cycle length of 500milliseconds.
 85. The method of claim 30, wherein steps(b-f) areperformed within the implanted cardioverter defibrillator device. 86.The method of claim 30, wherein electrograms are acquired from implantedelectrodes which are connected to the implanted cardioverterdefibrillator and are transmitted electronically from the implantedcardioverter defibrillator device to an external programmer, steps (b)(ii)-(v) are performed in the programmer,—test-shock times aretransmitted from the programmer to the cardioverter defibrillator andtest shocks are delivered by the implanted shock electrodes which areconnected to the implantable cardioverter defibrillator.
 87. The methodof claim 30 wherein (a) electrograms are acquired from implantedelectrodes which are connected to the implantable cardioverterdefibrillator and are transmitted electronically from the implantedcardioverter defibrillator to an external programmer, (b) steps (a) and(b) (ii)-(v) are performed in the programmer, (c) a computer screen onthe programmer displays one or more signals taken from a plurality of i)one or more surface ECG leads; ii) a plurality of telemeteredelectrograms from the implantable cardioverter defibrillator; iii) thedifferentiated electrogram; iv) the base timing point determined inclaim 30 (b) (ii); v) the timing point determined by maximum of thederivative of a T wave claim 30 (b) (iv); and vi) the base time intervalin claim 30 (b) (v), (d) an operator views the screen; and (e) if theoperator confirms the timing of timing points indicated in (a) (iii) and(a) (iv) of the present claim (using a computer input device such as amouse, trackball, or touch-screen pen), the test shock times aretransmitted from the programmer to the implantable cardioverterdefibrillator, which delivers test shocks via the implanted shockelectrodes; and (f) if the operator does not confirm the timing oftiming points indicated in (a) (iii) and (a) (iv) of the present claim,the operator adjusts the timing of one of these points (using a computerinput device such as a mouse, trackball, or touch-screen pen) resultingin an adjusted base time interval; causing (g) the programmer to makeadjustments in the base time interval and test-shock time correspondingto the base time interval plus one of the offset times; and (h) theadjusted test-shock time is transmitted from the programmer to thecardioverter defibrillator, and (i) the test shocks is delivered fromthe implantable cardioverter defibrillator to the implanted shockelectrodes which are connected to the heart.
 88. The method of claim 30,wherein electrograms are acquired from electrodes that are implanted inthe patient and are connected directly to an external implant-supportdevice, (a) steps (a) and (b) (ii)-(v) are performed in theimplant-support device, (b) a computer screen on the implant-supportdevice displays one or more signals taken from: i) one or more surfaceECG leads; ii) a plurality of electrograms transmitted from implantedelectrodes; iii) the differentiated electrogram; iv) the base timingpoint determined in claim 30 (b) (ii); v) the timing point determined bymaximum of the derivative of a T wave in claim 30 (b) (iv); and vi) thebase time interval in claim 30 (b) (v); (c) an operator views thescreen; and (d) if the operator confirms the timing of timing pointsindicated in (a) (iii) and (a) (iv) of the present claim, the test shockis delivered from the external implant-support device to the implantedshock electrodes which are connected to the heart; and (e) if theoperator does not confirm the timing of timing points indicated in (a)(iii) and (a) (iv) of the present claim, the operator adjusts the timingof one of these points resulting in an adjusted base time interval,causing (f) the implant support device to make an adjustment in thetest-shock time corresponding to the base time interval plus one of theoffset times; and (g) test shocks are delivered by the implant-supportdevice to implanted shock electrodes which are connected to the heart.89. The method of claim 30, wherein electrograms are acquired fromelectrodes that are implanted in the patient and are connected directlyto an external implant-support device, steps (a-d) are performed in theexternal implant-support device and test shocks are delivered from theexternal implant-support device to the implanted shock electrodes whichare connected to the heart.
 90. The method of claim 30, wherein thesensing steps are implemented with a plurality of electrodes, anddelivery of a test shock in step (b)(vi) occurs at a test-shock timerelating to the latest-peaking monophasic T-wave detected from anyelectrode.
 91. The method of claim 30, wherein the sensing steps areimplemented with a plurality of electrodes, and wherein the maximum ofthe first derivative of the T-wave with respect to time is detected fromthe electrode in which the derivative of the T-wave reaches its maximumvalue at the latest time.
 92. The method of claim 30, wherein at leastone implanted electrode is used to sense electrical activity of theheart.
 93. The method of claim 30, wherein the implantable cardioverterdefibrillator is electrically connected to a predetermined arrangementof implanted electrodes and communicates with a programmer via a meansselected from the group consisting of radio frequency and telemetry. 94.The method of claim 93, wherein the implanted electrodes comprise atleast two defibrillation electrodes, at least one of which isintravenously implanted within the heart, at least one implanted sensingelectrode, and at least one implanted pacing electrode.
 95. The methodof claim 82, wherein the step of detecting at least one maximumderivative of a T-wave is accomplished by selecting a beat from aplurality of paced beats of a pacing sequence of beats, and a detectedmaximum derivative of a T-wave is utilized to determine a test-shocktime at the end of the pacing sequence.
 96. The method of claim 82,wherein the step of detecting at least one maximum derivative of aT-wave is accomplished by calculating an average of a plurality of pacedbeats of a pacing sequence of beats, and the detected maximum derivativeof a T-wave is utilized to determine a test-shock time at the end of thepacing sequence.
 97. The method of claim 82, wherein the step ofdetecting at least one maximum derivative of a T-wave is accomplished byselecting the next-to-last paced beat of a plurality of paced beats in apacing sequence of beats, and the detected maximum derivative of aT-wave is utilized to determine a test-shock time at the end of thepacing sequence.
 98. The method of claim 82, wherein the step ofdetecting at least one maximum derivative of a T-wave is accomplished byselecting a beat from a plurality of paced beats of a pacing sequence ofbeats, and a detected maximum derivative of a T-wave is utilized todetermine a test-shock time at the end of the next pacing sequence. 99.The method of claim 82, wherein the step of detecting at least onemaximum derivative of a T-wave is accomplished by calculating an averageof a plurality of paced beats of a pacing sequence of beats, and thedetected maximum derivative of a T-wave is utilized to determine atest-shock time at the end of the next pacing sequence.
 100. The methodof claim 82, wherein the step of detecting at least one maximumderivative of a T-wave is accomplished by selecting the next-to-lastpaced beat of a plurality of paced beats in a pacing sequence of beats,and the detected maximum derivative of a T-wave is utilized to determinea test-shock time at the end of the next pacing sequence.
 101. Themethod of claim 75, wherein the step of detecting at least one maximumderivative of a T-wave is accomplished by selecting a beat in nativerhythm.
 102. The method of claim 75, wherein the step of detecting atleast one maximum derivative of a T-wave is accomplished by calculatingan average value from a plurality of native rhythm beats.
 103. Themethod of claim 75, wherein the step of detecting at least one maximumderivative of a T-wave is accomplished by selecting the last beat of aplurality of native rhythm beats in a sequence of native rhythm beats.104. The method of claims 101-103, further comprising the initial stepof measuring regularity of native rhythm, and if the rhythm is moreirregular than a predetermined threshold value, a. waiting apredetermined period of time before implementing step (b); b. after step(b) (vi), measuring the regularity of native rhythm; and c. if therhythm is sufficiently regular, delivering any T-wave test shock of step(b) (viii); and d. if the rhythm is not sufficiently regular,reinitiating the waiting period.
 105. The method of claim 30, wherein,if the timing of the maximum of the of the first derivative of theT-wave with respect to time cannot be reliably detected, comprising theadditional steps of: a. waiting a predetermined period of time; and b.repeating the detecting step (b).
 106. The method of claim 30, wherein avalue of the timing of the maximum derivative T-wave is determined asthe average value of a predefined number of beats, and is compared to avalue of the timing of the maximum of the first derivative of the T-wavewith respect to time measured on the beat prior to delivery of the testshock, and the test shock is aborted if the difference between these twovalues exceeds a predetermined amount.
 107. The method of claim 106,wherein the predetermined amount is 10-100 milliseconds.
 108. The methodof claim 107, wherein the predetermined amount is 20 milliseconds. 109.The method of claim 31, in which the increment and decrement values areeach a function of the test-shock strength.
 110. The method of claim 31,in which the specified number of times is between 0 and
 10. 111. Themethod of claim 31, in which the specified number of times is 2 or 3.112. The method of claim 31, in which the specified number of timesdepends on the outcomes with respect to fibrillation of all previoustest shocks delivered.
 113. The method of claim 31, further comprisingthe sub step of waiting a predetermined period of time before repeatingstep (b) at a higher test-shock strength.
 114. The method of claim 55,wherein the predetermined waiting period of time is between about 3minutes and about 5 minutes.
 115. The method claim 31, wherein asequence of one or more test shocks is delivered at only one shockstrength, and if fibrillation is not detected in step (b) by the fourthtest shock, the programmed shock strength of the implantablecardioverter defibrillator is set to a value that is a fixed incrementgreater than the test shock strength.
 116. An apparatus for determininga cardiac shock strength, comprising: (a) a sensor for sensing theelectrical activity of the heart, including the change in the T-wavewith respect to time of a cardiac signal and including fibrillation; and(b) a controller, connected to the sensor, which provides a test shockof a test-shock strength and at a test-shock time relating to the changein the T-wave with respect to time, and to determine the cardiac shockstrength as a function of the test-shock strength.
 117. An apparatus fordetermining and delivering a therapeutic cardiac shock, comprising: (a)a plurality of electrodes, at least one electrode being adapted forsensing cardiac signals and at least one electrode being adapted fordelivering shocks to the heart; (b) a shock subsystem connected to theat least one electrode for delivering shocks and which is capable ofgenerating test shocks and therapeutic cardiac shocks; and (c) a ULVsubsystem connected to the shock subsystem and for providing test-shockinformation to the shock subsystem, the test-shock information includingtest-shock strength and test-shock time relating to a change in one ormore cardiac signals with respect to time, and for determining the shockstrength of the therapeutic cardiac shocks as a function of thetest-shock strength.
 118. An implantable cardioverter defibrillatorsystem for determining and delivering an optimal programmed first-shockstrength based on the upper limit of vulnerability, comprising: (a) aplurality of implantable electrodes; (b) a shock delivery subsystem,connected to the electrodes; and (c) a ULV subsystem comprising; i) asensor, connected to the electrodes, for sensing the electrical activityof the heart, including a change with respect to time of the T-wave of acardiac signal and including the presence of fibrillation; ii) a timerconnected to the sensor for providing a series of shock times, timedrelative to the maximum derivative of the T-wave; iii) a test-shockdriver, connected to the timer, for transmitting timing and amplitudeinformation regarding T-wave test shocks; iv) a memory unit, connectedto the test shock driver and the shock subsystem, for storingprogrammable values such as pacing cycle length, timing intervals, aninitial shock strength, and values for incrementing and decrementingshock strength; and v) a controller, connected to the sensor, test-shockdriver, and shock subsystem for incrementally varying shock strength andthe shock times; whereby the system provides a test shock having a shockstrength and shock time selected by the controller; (d) whereby: (i) theshock subsystem delivers an initial test shock to the heart at aninitial shock strength and an initial shock time; and if the heart doesnot fibrillate (ii) the system delivers a sequence of test shocks to theheart at the same shock strength and different shock times; and if theheart does not fibrillate (iii) the system decreases the shock strength,a strength decrement and delivers test shocks at a sequence ofintervals; and if the heart does not fibrillate (iv) the system repeatssteps (d) (i)-(iii) until the heart fibrillates, whereby the shockstrength of the test shock immediately prior to the test shock thatinduces fibrillation represents the upper limit of vulnerability, andwhereby the optimal programmed first shock strength of an implantablecardioverter defibrillator system is predicted by a fixed increment inrelation to the energy level determined to be the upper limit ofvulnerability.
 119. The system of claim 118, wherein the system operateswhen the heart is in its native rhythm.
 120. The system of claim 118,wherein the system operates when the heart is paced, the system furthercomprising a pacer for overdrive pacing the heart, the timer beingelectrically connected to the pacer and shock times further being timedin relation to one or more pacing spikes from the pacer according to atime delay.
 121. The system of claim 118, wherein the programmed shockstrength of an implantable cardioverter defibrillator is a valueincrementally higher than the upper limit of vulnerability.
 122. Thesystem of claim 118, wherein the strength decrement is at least 2Joules.
 123. The system of claim 118, wherein the timer provides atleast four time delays comprising time delays measured from a base time,measured from a predetermined point on an electrogram to a the maximumof the first derivative of the T-wave with respect to time, plus anoffset interval ΔT.
 124. The system of claim 123, wherein the offsetintervals are: 0 milliseconds before the maximum derivative of theT-wave, 20 milliseconds before the maximum derivative of the T-wave, 40milliseconds before the maximum derivative of the T-wave, and 20milliseconds after the maximum derivative of the T-wave.
 125. The systemof claim 123, wherein the offset intervals are: 0 milliseconds beforethe maximum derivative of the T-wave, 20 milliseconds before the maximumderivative of the T-wave, 20 milliseconds after the maximum derivativeof the T-wave, and 40 milliseconds after the maximum derivative of theT-wave.
 126. The system of claim 118, wherein the electrode arrangementconsists of implanted electrodes.
 127. The system of claim 126, whereinthe implanted electrodes includes at least one intracardiac electrode.128. The system of claim 126, wherein the implanted electrodes includesat least one intravascular electrode.
 129. The system of claim 126,wherein the implanted electrodes includes at least one subcutaneouselectrode.
 130. The system of claim 126, wherein the implantedelectrodes includes at least one submuscular electrode.
 131. The systemof claim 126, wherein the implanted electrodes includes at least oneepicardial electrode.
 132. The system of claim 126, wherein theelectrodes include at least one cutaneous electrode.
 133. The system ofclaim 118, wherein a sequence of one or more test shocks are deliveredat only one shock strength, and if fibrillation is not detected, theprogrammed shock strength is set to a value that is a fixed incrementgreater than the test shock strength.
 134. The system of claim 133, inwhich the energy level is 15 Joules.
 135. The system of claim 133,wherein the fixed increment is 5 J above the energy level.